The present invention relates generally to methods of performing medical procedures, methods of making compositions useful in such medical procedures, and apparatus useful in such methods. In particular, the present invention is directed towards methods of making compositions useful in certain medical procedures, and methods of performing medical procedures in which a composition promotes bone growth when the composition is positioned in the vicinity of a bone of a mammal. The present invention also is directed towards apparatus that are useful in making such compositions, and in performing such medical procedures.
Human bone includes a solid mineral phase and an organic matrix that is between 90% and 95% type I collagen. The mineral phase includes, inter alia, calcium and phosphate. The mechanical properties of bone are related to its specific type of construction and internal architecture. Although bone may be relatively light, it also may have a relatively high tensile strength. This combination of high strength coupled with relatively low weight results from, inter alia, the hollow, tubular shape of bone, the layering of bone tissue, and the internal buttressing within the organic matrix. Bone tissue may supplant membranous or fibrous tissue by a mechanism referred to as “intramembranous ossification.” Bone tissue only grows by appositional growth, e.g., the deposition of a new organic matrix on the surface of the bone by adjacent surface cells. A damaged bone repairs itself through a multiphase process. Initially, bone repair begins with an inflammatory phase, involving extensive tearing of the membrane surrounding the bone (the periosteum), rupturing of blood vessels and extensive hemorrhaging. Typically, this leads to a secondary inflammatory response of white blood cells (e.g., polymorphonuclear leukocytes, macrophages, and mononuclear cells), in an effort to prevent infection. Pluripotential mesenchymal cells from the soft tissue and within the bone marrow give rise to the osteoblast cells that synthesize bone.
Known bone replacement technologies can be divided into three transitional matrix categories. The first category relies on replacing bone with either autogenous, homologous, heterologous, or decalcified bone, followed by remodeling. As referred to herein, the term “remodeling” will be understood to mean the process by which bone is continually built and resorbed within the body. This first category may be problematic, however, because of difficulties inherent in harvesting the replacement bone, as well as the risk of transmitting blood-borne pathogens into the body of the recipient. The second category involves synthetic bone replacement, e.g., replacing bone with a bone-like mineral (e.g., crystalline hydroxyapatite or calcium pyrophosphate), followed by remodeling. Conventional synthetic bone replacement may be problematic, however, because the replacement material may have poor tensile strength and may adhere poorly to the surrounding bone. The third category relies on replacing bone with a composition that maintains its chemical and mechanical properties without change or subsequent remodeling (e.g., titanium, stainless steel, PMMA); nevertheless, this category is problematic because, inter alia, it does not allow for the growth of new bone.
Conventional biological materials (e.g., those comprising poly(lactic acid)) also have been considered for use in bone replacement procedures. However, such materials may degrade over a particular period of time, irrespective of whether new bone has formed in the vicinity of the material, thereby leaving undesirable voids that may limit the stability of surrounding structures within the body of the mammal.
Additionally, certain conventional bone replacement materials may produce a substantial exotherm once placed in the body of a mammal. Generally, the exotherm is caused by curing (e.g., continued polymerization) of the conventional bone replacement material within the body. The exotherm produced by certain conventional bone replacement materials may reach temperatures above 45° C., which may, inter alia, cause adjacent tissue to necrose. Rapid-cure conventional bone replacement materials (e.g., conventional bone replacement materials that may be cured within the body within 1-5 minutes after exposure to an energy source that facilitates curing) are particularly likely to produce such undesirable exotherms reaching such undesirably high temperatures.
Traditional methods for preparation of conventional bone replacement materials often involve the use of glass ampoules, within which are disposed certain chemical components. The ampoules are cracked to release the components, which subsequently are reacted to form the conventional bone replacement material. Glass ampoules are problematic for a number of reasons. First, they must be cracked in order to release the compounds stored within, which poses a safety hazard in that the cracked glass may puncture the skin of the technician handling the ampoule. Moreover, the cracking of the glass creates glass fragments that may fall back into the ampoule, which may cause them to become incorporated within the bone replacement material. Further, because the ampoules lack a dispensing means capable of positively displacing the compound stored therein, the ampoules must be inverted and poured. Often, this is a time-consuming process, because the stored compounds may be quite viscous. Air bubbles also may become entrained in the stored compounds during the pouring process. Additionally, some portion of the stored compounds generally will remain within the ampoule at the completion of the pouring process, and cannot be displaced. In addition to wasting material, this is undesirable because proper formulation of conventional bone replacement materials often requires mixing of the entirety of the contents of the ampoules; if a portion of one or more components remains within the ampoule, the resulting bone replacement material will not be properly formulated.
Further, conventional methods of preparing bone replacement material often involve elaborate vapor containment measures. Such measures commonly are employed because, inter alia, certain bone replacement materials that are PMMA-based may be extremely toxic. Furthermore, certain blood-based products may create a risk of blood-borne-pathogen transmission or contamination. This may be problematic, because not all operating rooms are equipped with vacuum apparatus, and because expensive accessory equipment may be required.